diabetes insipidus

Question 1

definition

Answer 1

metabolic disorder causing defective ability to concentrate urine in kidneys -> production of large amounts of dilute urine.
can be caused by deficiency of arginine vasopressin (AVP) (aka ADH) which is produced by the hypothalamus and secreted via posterior pituitary. or caused by resistance to action of AVP in renal collecting ducts.

** AVP made in hypothalamus -> go to posterior pituitary gland via pituitary stalk -> stored here for release into systemic circulation. released in response to osmoreceptor sensing of hyperosmolality and baroregulated mechanisms

manifests clinically as polydipsia, polyuria, hypotonic urine

Question 2

types of DI

Answer 2

central DI: deficiency in production of AVP (something up with the hypothalamus or pituitary)

nephrogenic DI: problem with the action of AVP in the kidneys/not responsive to AVP (renal impairment due to chronic diseases, AVP receptor pathway mutations, long term lithium therapy use)

DI in pregnancy: transient central DI can happen due to decreased osmotic threshold for thirst and ACPA release, and decrease in serum osmolality. also a 4x increase in metabolic clearance of AVP due to placental production of vasopressinase/oxytocinase.

Question 3

triple phase response in DI

Answer 3

1. polyuric phase: decrease in AVP -> immediate increase in urine output with reduced urine osmolality. (4-5 days)
2. antidiuretic phase: axonal necrosis of AVP-secreting neurons -> uncontrolled AVP release -> reduction in urinary output, increase in urine osmolality (may be associated with hyponatraemia secondary to SIADH) (5-6 days)
3. permanent central DI: neuronal death with cessatioin of AVP production and depletion of AVP reserve

Question 4

signs and symptoms

Answer 4

• polyuria
• polydipsia
• nocturia
• non-specific CNS symptoms of hypernatraemia (lethargy, irritability, restlessness, spasticity, hyper-reflexia) (severe hypernatraemia -> delirium, seizures, coma)
• signs of volume depletion (dry mucous membranes, poor skin turgor, tachycardia, hypotension, if severe -> shock)
• muscle twitching
• hyperthermia
• visual field defects –> can indicate pituitary lesion
• focal motor deficits –> intracranial tumours
• sensorineural deafness –> may be wolfram’s syndrome (DI, DM, optic atrophy, deafness)
• skin rash –> red papular rash may be langerhans’ cell histiocytosis causing central DI. lupus pernio or erythema nodosum may be sarcoidosis causing central or nephrogenic DI)

Question 5

risk factors

Answer 5

• pituitary surgery
• carniopharyngioma (benign tumour near pituitary)
• pituitary stalk lesions
• traumatic brain injury
• congenital pituitary abnormalities
• medication (in nephrogenic DI) (demeclocycline, cisplatin, colchicine, rifampin etc.)
• autoimmune disease (central DI associated with polyendocrine autoimmune disorders e.g. hashimoto’s and type 1 DM)
• wolfram’s syndrome
• family history
• pregnancy
• cerbrovascular accident (central DI can happen after subarach haemorrhage, esp if involving anterior communicating artery which supplies anterior hypothalamus)
• previous CNS infections (central DI can be a late complication of meningitis or encephalitis)

other risk factors for nephrogenic DI:
sickle cell anemia
renal sarcoidosis 
renal amyloidosis
poorly controlled DM
chronic hypercalcaemia or hyperkalaemia 
protein malnutrition
previous release of ureteric obstruction

Question 6

investigations

Answer 6

1st investigations:

• urine osmolality
• serum osmolality
• serum sodium => may be elevated in DI
• serum calcium (chronic hypercalcaemia associated with nephrogenic DI)
• serum potassium (chronic hypokalaemia associated with nephrogenic DI)
• urine dipstick (check for glycosuria to exclude DM as cause of polyuria. although DM and DI can coexist)
• 24hr urine collection for volume
• serum urea nitrogen => elevated in patients with volume depletion
• serum glucose (for baseline, also to exclude DM)

others:

• water deprivation test
• AVP stimulation test
• 3% hypertonic saline infusion test
• MRI pituitary (with contrast)
• serum TSH and free T4 (looking for hashimoto’s)
• antithyroid peroxidase autoantibodies (looking for hashimoto’s)
• genetic studies (WSF1 gene mutation associated with central DI, mutations in AVP-V2 receptor pathway commin in nephrogenic DI)

Question 7

treatment

Answer 7

hypernatraemia: oral/IV fluids

central DI: desmopressin + fluids if necessary

nephrogenic DI: maintain adequate fluid intake  
treat underlying cause
sodium restriction (to reduce urinary output) and/or pharmacotherapy -- hydrochlorothiazide or indometacin (but indimethacin can have serious GI and renal side effects)

Question 8

complications

Answer 8

• hypernatraemia
• thrombosis (hypernatraemia and dehydration increase thrombosis risk)
• bladder and renal dysfunction (due to excessive urinary volume, need frequent renal profiles and renal or bladder imaging)
• iatrogenic hyponatraemia